To support critical NIH-funded biomedical research at Scripps Institution of Oceanography (SIO) / University of California, San Diego (UCSD), this proposal details need, provides justification and requests funding for a combined high resolution HPLC and high resolution time-of-flight (TOF) mass spectrometer system for rapid, efficient separation of sample components and accurate mass determination of a wide range of molecules derived from this research. The analytical instrumentation includes a high resolution HPLC that can readily accommodate less than 2 micron particle stationary phases operated at pressures up to 9000 psi (600 bar), which provide for effective and efficient several minute analyses of moderately to highly complex mixtures. The requested instrumentation also includes a high resolution (HR) TOF mass spectrometer (MS) with a highly sensitive electrospray ionization source or a combined atmospheric pressure electrospray and chemical ionization source which yields molecular formulas with sub-1 ppm accuracy of unknown and known compounds ranging in polarity from nonpolar organic molecules to highly-charged water-soluble molecules with mass-to-charge ratios of up to 20,000. In a multi-user, walk- up environment that is supported by user-friendly open-access software, this LC / HRMS system will be utilized extensively for the rapid determination of molecular formulas for novel marine natural products, efficient dereplication of known natural products from marine bacteria and cyanobacteria, identification of microbial metabolites in low concentrations following genetic manipulation, and structure determination of semisynthetic, synthetic and genetically engineered natural products. PUBLIC HEALTH RELEVANCE: This application requests NIH support for the replacement of an aging and obsolete Hewlett-Packard (Agilent) 1100 low resolution LC-MS with an updated Agilent 6230AA LC-MS to be used by NIH sponsored marine biomedical researchers. The proposed instrument, which will be located in the CMBB core, will provide molecular formula data and dramatically shorten analysis times, and accelerate the research of more than 40 faculty, staff, students and postdocs within the Center for Marine Biotechnology and Biomedicine (CMBB) at SIO.